The main objective of the proposed research is to further our understanding of the relationships between renal metabolism and renal function and the regulation of these processes. In order to achieve this objective we propose to examine the role of enzyme interactions in the hormonal regulation of gluconeogenesis, glycolysis and transport systems in this tissue. The hormonal stimulation of amino acid transport may be integrated with the activation of intracellular multienzyme systems which utilize these transported substances. These processes may be integrated at the level of 3' -5'-cyclic AMP by the coordinated action of protein kinase acting at the membrane and in the cytosol. The role of 3' -5' -cyclic AMP-dependent phosphorylation and dephosphorylation of specific soluble and membrane bound enzymes involved in renal tubular transport of amino acids and glucose and glyconeogenesis will be investigated. The approach will involve studies with isolated enzymes and reconstructed multienzyme systems. These processes will also be examined with isolated kidney epithelial cells maintained in tissue culture. The influence of parathyroid hormone, epinephrine and antidiuretic hormone on transport, gluconeogenesis and the extent of phosphorylation and activity of selected regulatory enzymes in these preparations will be examined. The allosteric, binding and kinetic effects observed in well-defined isolated enzyme systems will be examined with isolated cell preparations maintained with various hormones under glycolytic or gluconeogenic conditions to determine whether these effects and interactions can also be observed in intact cells.